Mechanisms of Ozone-Induced Alterations in Efferocytosis and Phagocytosis
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|ClinicalTrials.gov Identifier: NCT03646877|
Recruitment Status : Suspended (COVID 19)
First Posted : August 24, 2018
Last Update Posted : May 14, 2020
The purpose of this research study to understand how environmental and genetic factors may be involved in lung function. Healthy Study participants will undergo a 1-day screening that includes a blood draw and breathing testing, return for a two-day series of testing to include blood draw, and brief breathing test before and after an inhaled challenge with either filtered air (FA) or ozone (O3). Participants return the next day for a brief breathing test, a blood draw and a procedure called bronchoscopy performed under conscious sedation to evaluate the lung after the challenge.
Participants then return 18 - 20 days later to repeat the two-day series of testing to be challenged with the exposure not received on the first series, (FA or O3). Each visit will take about 3 - 3.5 hours. Follow-up phone calls from the study team will occur at 24 hours after each 2-day test series. Total study duration is about one to one-and a half months.
|Condition or disease||Intervention/treatment||Phase|
|Healthy||Drug: Ozone Other: Filtered Air||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||70 participants|
|Intervention Model:||Crossover Assignment|
|Official Title:||Mechanisms of Ozone-Induced Alterations in Efferocytosis and Phagocytosis|
|Actual Study Start Date :||February 19, 2019|
|Estimated Primary Completion Date :||January 31, 2024|
|Estimated Study Completion Date :||January 31, 2024|
Experimental: Ozone (O3)
The O3 level during the exposures will be 200 ppb, which has previously been used in human exposure studies without short or long term, untoward side effects (and comparable to peak levels attained during the summer in the Raleigh-Durham area of North Carolina) (REF - Bromberg review).
Subjects will perform alternating 15 minutes rest with 15 minutes treadmill walk exercise periods for 135 minutes in while breathing Ozone (O3).
Other Name: O3
Placebo Comparator: Filtered Air (FA)
Control will be treadmill walk with filtered room air in chamber.
Other: Filtered Air
Subjects will perform alternating 15 minutes rest with 15 minutes treadmill walk exercise periods for 135 minutes in while breathing filtered air.
- change in ozone induced efferocytosis of lung macrophages (ability to clear dead or dying cells) [ Time Frame: Baseline, 21 days ]Efferocytosis is defined by determining the number of apoptotic PMNs phagocytized by alveolar macrophages (BAL cytospins) versus the total number of macrophages ('efferocytic index')
- Change in ozone induced phagocytosis of lung macrophages (ability to clear debris or bacteria) [ Time Frame: Baseline, 21 days ]Bronchoalveolar macrophages are incubated with pHrodo™ dye-labeled particles. Macrophage phagocytosis will be defined by determining the number of macrophages that contain fluorescent particles versus the total macrophages Cell free hemoglobin and soluble CD163 - both are measured by commercial ELISA kit
- Change in ozone induced increase in cell free hemoglobin in bronchoalveolar lavage fluid and serum [ Time Frame: Baseline, 21 days ]Measured by enzyme-linked immunosorbent assay (ELISA)
- Change in ozone induced increase in soluble CD163 in bronchoalveolar lavage fluid and serum [ Time Frame: Baseline, 21 days ]Measured by enzyme-linked immunosorbent assay (ELISA)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03646877
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||Robert Tighe, MD||Duke University|